Numerous investigations have provided evidence that the secretory immune system plays a primary role in protecting the host against infections associated with mucosal surfaces, such as dental caries. The first major objective of the research to be performed in the next year is to determine the mechanism(s) involved in the induction and regulation of IgA immune responses to orally administered antigens. Specifically, the role of Peyer's patch (PP) accessory cells and T cells will be assessed for their ability to influence IgA immune responses in vitro. Emphasis will be placed on cloned murine PP T helper cells for IgA responses (PP Th A) and their Fc receptors to establish the mechanism by which they regulate IgA responses in purified B cell cultures. The second major objective is to determine the most effective means of inducing protective immunity against dental caries and to determine the mechanisms by which secretory IgA antibodies affect protection against Streptococcus mutans - induced dental caries. Specifically, the effectiveness of oral adjuvants for enhancing and prolonging secretory IgA immune responses protective against dental caries formation will be assessed. For these studies, gnotobiotic rats will be given purified S. mutans antigens, including serotype carbohydrate, glucosyltransferase, or surface protein associated antigen, in adjuvants by gastric intubation. The primary oral adjuvants to be studied will be liposomes containing lipophilic muramyl dipeptide (MDP) derivatives. Following oral immunization of rats with antigen and adjuvant, the magnitude, specificity, and duration of the secretory immune responses in saliva will be determined and correlated with the extent of caries protection. The level, isotype and specificity of any systemic response will also be determined. An analysis of secretory and systemic immune responses, histopathology, and dental caries protection should suggest a useful vaccine effective against dental caries for use in humans.